Beta blocker

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Beta blockers
Drug class
Propranolol-2D-skeletal.png
Skeletal formula of propranolol, the first clinically successful beta blocker
Class identifiers
Synonyms beta-blockers, β-blockers, beta-adrenergic blocking agents, beta antagonists, beta-adrenergic antagonists, beta-adrenoreceptor antagonists, beta adrenergic receptor antagonists
Use Hypertension, arrhythmia, etc.
ATC code C07
Biological target beta receptors
Clinical data
Drugs.com Drug Classes
Consumer Reports Best Buy Drugs
WebMD MedicineNet   RxList
External links
MeSH D000319
In Wikidata

Beta blockers (beta-blockers, β-blockers, etc.) are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack (myocardial infarction) after a first heart attack (secondary prevention). [1] They are also widely used to treat high blood pressure (hypertension), although they are no longer the first choice for initial treatment of most patients. [2]

Myocardial infarction interruption of blood supply to a part of the heart

Myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck, or jaw. Often it occurs in the center or left side of the chest and lasts for more than a few minutes. The discomfort may occasionally feel like heartburn. Other symptoms may include shortness of breath, nausea, feeling faint, a cold sweat, or feeling tired. About 30% of people have atypical symptoms. Women more often present without chest pain and instead have neck pain, arm pain, or feel tired. Among those over 75 years old, about 5% have had an MI with little or no history of symptoms. An MI may cause heart failure, an irregular heartbeat, cardiogenic shock, or cardiac arrest.

Hypertension high blood pressure

Hypertension, also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure typically does not cause symptoms. Long-term high blood pressure, however, is a major risk factor for coronary artery disease, stroke, heart failure, atrial fibrillation, peripheral vascular disease, vision loss, chronic kidney disease, and dementia.

Contents

Beta blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) on adrenergic beta receptors, of the sympathetic nervous system, which mediates the fight-or-flight response. [3] [4] Some block activation of all types of β-adrenergic receptors and others are selective for one of the three known types of beta receptors, designated β1, β2 and β3 receptors. [5] β1-adrenergic receptors are located mainly in the heart and in the kidneys. [4] β2-adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle. [4] β3-adrenergic receptors are located in fat cells. [6]

Catecholamine 4-(2-aminoethyl)pyrocatechol and derivatives formed by substitution

A catecholamine is a monoamine neurotransmitter, an organic compound that has a catechol and a side-chain amine.

Adrenaline hormone, neurotransmitter and medication. Epinephrine is normally produced by both the adrenal glands and certain neurons

Adrenaline, also known as epinephrine, is a hormone, neurotransmitter, and medication. Adrenaline is normally produced by both the adrenal glands and certain neurons. It plays an important role in the fight-or-flight response by increasing blood flow to muscles, output of the heart, pupil dilation response, and blood sugar level. It does this by binding to alpha and beta receptors. It is found in many animals and some single cell organisms. Napoleon Cybulski first isolated adrenaline in 1895.

Norepinephrine chemical compound

Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone and neurotransmitter. The name "noradrenaline", derived from Latin roots meaning "at/alongside the kidneys", is more commonly used in the United Kingdom; in the United States, "norepinephrine", derived from Greek roots having that same meaning, is usually preferred. "Norepinephrine" is also the international nonproprietary name given to the drug. Regardless of which name is used for the substance itself, parts of the body that produce or are affected by it are referred to as noradrenergic.

Beta receptors are found on cells of the heart muscles, smooth muscles, airways, arteries, kidneys, and other tissues that are part of the sympathetic nervous system and lead to stress responses, especially when they are stimulated by epinephrine (adrenaline). Beta blockers interfere with the binding to the receptor of epinephrine and other stress hormones, and weaken the effects of stress hormones.

Heart organ for the circulation of blood in animal circulatory systems

The heart is a muscular organ in most animals, which pumps blood through the blood vessels of the circulatory system. Blood provides the body with oxygen and nutrients, as well as assisting in the removal of metabolic wastes. In humans, the heart is located between the lungs, in the middle compartment of the chest.

Artery blood vessels that carry blood away from the heart

An artery is a blood vessel that takes blood away from the heart to all parts of the body. Most arteries carry oxygenated blood; the two exceptions are the pulmonary and the umbilical arteries, which carry deoxygenated blood to the organs that oxygenate it. The effective arterial blood volume is that extracellular fluid which fills the arterial system.

Kidney internal organ in most animals, including vertebrates and some invertebrates

The kidneys are two bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about 11 centimetres (4.3 in) in length. They receive blood from the paired renal arteries; blood exits into the paired renal veins. Each kidney is attached to a ureter, a tube that carries excreted urine to the bladder.

In 1964, James Black [7] synthesized the first clinically significant beta blockers—propranolol and pronethalol; it revolutionized the medical management of angina pectoris [8] and is considered by many to be one of the most important contributions to clinical medicine and pharmacology of the 20th century. [9]

James Black (pharmacologist) Scottish doctor and pharmacologist

Sir James Whyte Black was a Scottish physician and pharmacologist. Black established a Veterinary Physiology department at the University of Glasgow, where he became interested in the effects of adrenaline on the human heart. He went to work for ICI Pharmaceuticals in 1958 and, while there, developed propranolol, a beta blocker used for the treatment of heart disease. Black was also responsible for the development of cimetidine, an H2 receptor antagonist, a drug used to treat stomach ulcers. He was awarded the Nobel Prize for Medicine in 1988 for work leading to the development of propranolol and cimetidine.

Propranolol beta blocker drug

Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety, and essential tremors. It is used to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks. It can be taken by mouth or by injection into a vein. The formulation that is taken by mouth comes in short-acting and long-acting versions. Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken by mouth.

Pronethalol chemical compound

Pronethalol was an early non-selective beta blocker clinical candidate. It was never used clinically due to carcinogenicity in mice, which was thought to result from formation of a carcinogenic naphthalene epoxide metabolite.

For the treatment of primary hypertension, meta-analyses of studies which mostly used atenolol have shown that although beta blockers are more effective than placebo in preventing stroke and total cardiovascular events, they are not as effective as diuretics, medications inhibiting the renin–angiotensin system (e.g., ACE inhibitors), or calcium channel blockers. [10] [11] [ needs update ] [12] [13]

Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Other uses include the prevention of migraines and treatment of certain irregular heart beats. It is taken by mouth or by injection into a vein. It can also be used with other blood pressure medications.

Placebo substance or treatment of no therapeutic value

A placebo is a substance or treatment of no intended therapeutic value. Common placebos include inert tablets, inert injections, sham surgery, and other procedures.

Stroke Medical condition where poor blood flow to the brain causes cell death

A stroke is a medical condition in which poor blood flow to the brain results in cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both result in parts of the brain not functioning properly. Signs and symptoms of a stroke may include an inability to move or feel on one side of the body, problems understanding or speaking, dizziness, or loss of vision to one side. Signs and symptoms often appear soon after the stroke has occurred. If symptoms last less than one or two hours it is known as a transient ischemic attack (TIA) or mini-stroke. A hemorrhagic stroke may also be associated with a severe headache. The symptoms of a stroke can be permanent. Long-term complications may include pneumonia or loss of bladder control.

Medical uses

Large differences exist in the pharmacology of agents within the class, thus not all beta blockers are used for all indications listed below.

Indications for beta blockers include:

Atrial fibrillation abnormal heart rhythm characterized by rapid and irregular beating

Atrial fibrillation is an abnormal heart rhythm characterized by rapid and irregular beating of the atria. Often it starts as brief periods of abnormal beating which become longer and possibly constant over time. Often episodes have no symptoms. Occasionally there may be heart palpitations, fainting, lightheadedness, shortness of breath, or chest pain. The disease is associated with an increased risk of heart failure, dementia, and stroke. It is a type of supraventricular tachycardia.

Essential tremor Movement disorder that causes involuntary tremors

Essential tremor is a progressive neurological disorder that is also the most common movement disorder. The cause of the condition is currently unknown. It typically involves a tremor of the arms, hands or fingers but sometimes involves the head, vocal cords or other body parts during voluntary movements such as eating and writing. It is distinct from Parkinson's disease—and often misdiagnosed as such—although some individuals have both conditions. Essential tremor is commonly described as an action tremor or postural tremor rather than a resting tremor, such as is seen in Parkinson’s, which is usually not included among its symptoms.

Beta blockers have also been used for:

Congestive heart failure

Although beta blockers were once contraindicated in congestive heart failure, as they have the potential to worsen the condition due to their effect of decreasing cardiac contractility, studies in the late 1990s showed their efficacy at reducing morbidity and mortality. [19] [20] [21] Bisoprolol, carvedilol, and sustained-release metoprolol are specifically indicated as adjuncts to standard ACE inhibitor and diuretic therapy in congestive heart failure, although at doses typically much lower than those indicated for other conditions. Beta blockers are only indicated in cases of compensated, stable congestive heart failure; in cases of acute decompensated heart failure, beta blockers will cause a further decrease in ejection fraction, worsening the patient's current symptoms.

Beta blockers are known primarily for their reductive effect on heart rate, although this is not the only mechanism of action of importance in congestive heart failure.[ citation needed ] Beta blockers, in addition to their sympatholytic β1 activity in the heart, influence the renin–angiotensin system at the kidneys. Beta blockers cause a decrease in renin secretion, which in turn reduces the heart oxygen demand by lowering extracellular volume and increasing the oxygen-carrying capacity of blood. Heart failure characteristically involves increased catecholamine activity on the heart, which is responsible for a number of deleterious effects, including increased oxygen demand, propagation of inflammatory mediators, and abnormal cardiac tissue remodeling, all of which decrease the efficiency of cardiac contraction and contribute to the low ejection fraction. [22] Beta blockers counter this inappropriately high sympathetic activity, eventually leading to an improved ejection fraction, despite an initial reduction in ejection fraction.

Trials have shown beta blockers reduce the absolute risk of death by 4.5% over a 13-month period. In addition to reducing the risk of mortality, the numbers of hospital visits and hospitalizations were also reduced in the trials. [23]

Anxiety

Officially, beta blockers are not approved for anxiolytic use by the U.S. Food and Drug Administration. [24] However, many controlled trials in the past 25 years indicate beta blockers are effective in anxiety disorders, though the mechanism of action is not known. [25] The physiological symptoms of the fight-or-flight response (pounding heart, cold/clammy hands, increased respiration, sweating, etc.) are significantly reduced, thus enabling anxious individuals to concentrate on the task at hand.

Musicians, public speakers, actors, and professional dancers have been known to use beta blockers to avoid performance anxiety, stage fright, and tremor during both auditions and public performances. The application to stage fright was first recognized in The Lancet in 1976, and by 1987, a survey conducted by the International Conference of Symphony Orchestra Musicians, representing the 51 largest orchestras in the United States, revealed 27% of its musicians had used beta blockers and 70% obtained them from friends, not physicians. [26] Beta blockers are inexpensive, said to be relatively safe, and on one hand, seem to improve musicians' performances on a technical level, while some, such as Barry Green, the author of "The Inner Game of Music" and Don Greene, a former Olympic diving coach who teaches Juilliard students to overcome their stage fright naturally, say the performances may be perceived as "soulless and inauthentic". [26]

Cardiac surgery

The use of beta blockers around the time of cardiac surgery decreases the risk of heart dysrhythmias. [27] Starting them around the time of other types of surgery, however, may worsen outcomes. [27]

Performance-enhancing use

Because they promote lower heart rates and reduce tremors, beta blockers have been used in professional sports where high accuracy is required, including archery, shooting, golf [28] and snooker. [28] Beta blockers are banned by the International Olympic Committee. [29] In the 2008 Summer Olympics, 50-metre pistol silver medalist and 10-metre air pistol bronze medalist Kim Jong-su tested positive for propranolol and was stripped of his medals. [30]

For similar reasons, beta blockers have also been used by surgeons. [31]

Adverse effects

Adverse drug reactions associated with the use of beta blockers include: nausea, diarrhea, bronchospasm, dyspnea, cold extremities, exacerbation of Raynaud's syndrome, bradycardia, hypotension, heart failure, heart block, fatigue, dizziness, alopecia (hair loss), abnormal vision, hallucinations, insomnia, nightmares, sexual dysfunction, erectile dysfunction and/or alteration of glucose and lipid metabolism. Mixed α1/β-antagonist therapy is also commonly associated with orthostatic hypotension. Carvedilol therapy is commonly associated with edema. [32] Due to the high penetration across the blood–brain barrier, lipophilic beta blockers, such as propranolol and metoprolol, are more likely than other less lipophilic beta blockers to cause sleep disturbances, such as insomnia, vivid dreams and nightmares. [33]

Adverse effects associated with β2-adrenergic receptor antagonist activity (bronchospasm, peripheral vasoconstriction, alteration of glucose and lipid metabolism) are less common with β1-selective (often termed "cardioselective") agents, but receptor selectivity diminishes at higher doses. Beta blockade, especially of the beta-1 receptor at the macula densa, inhibits renin release, thus decreasing the release of aldosterone. This causes hyponatremia and hyperkalemia.

Hypoglycemia can occur with beta blockade because β2-adrenoceptors normally stimulate glycogen breakdown (glycogenolysis) in the liver and pancreatic release of the hormone glucagon, which work together to increase plasma glucose. Therefore, blocking β2-adrenoceptors lowers plasma glucose. β1-blockers have fewer metabolic side effects in diabetic patients; however, the fast heart rate that serves as a warning sign for insulin-induced low blood sugar may be masked, resulting in hypoglycemia unawareness. This is termed beta blocker induced hypoglycemia unawareness. Therefore, beta blockers are to be used cautiously in diabetics. [34]

A 2007 study revealed diuretics and beta blockers used for hypertension increase a patient's risk of developing diabetes mellitus, while ACE inhibitors and angiotensin II receptor antagonists (angiotensin receptor blockers) actually decrease the risk of diabetes. [35] Clinical guidelines in Great Britain, but not in the United States, call for avoiding diuretics and beta blockers as first-line treatment of hypertension due to the risk of diabetes. [36]

Beta blockers must not be used in the treatment of selective alpha-adrenergic agonist overdose. The blockade of only beta receptors increases blood pressure, reduces coronary blood flow, left ventricular function, and cardiac output and tissue perfusion by means of leaving the alpha-adrenergic system stimulation unopposed.[ medical citation needed ] Beta blockers with lipophilic properties and CNS penetration such as metoprolol and labetalol may be useful for treating CNS and cardiovascular toxicity from a methamphetamine overdose. [37] The mixed alpha- and beta blocker labetalol is especially useful for treatment of concomitant tachycardia and hypertension induced by methamphetamine. [38] The phenomenon of "unopposed alpha stimulation" has not been reported with the use of beta blockers for treatment of methamphetamine toxicity. [38] Other appropriate antihypertensive drugs to administer during hypertensive crisis resulting from stimulant overdose are vasodilators such as nitroglycerin, diuretics such as furosemide, and alpha blockers such as phentolamine. [39]

Contraindications

Asthma

Beta blockers are contraindicated in patients with asthma as stated in the British National Formulary 2011.[ citation needed ] The 2007 National Heart, Lung, and Blood Institute (NHLBI) asthma guidelines recommend against the use of non-selective beta blockers in asthmatics, while allowing for the use of cardioselective beta blockers. [40] :182

Cocaine

They should also be avoided in patients with a history of cocaine use or in cocaine-induced tachycardia.[ citation needed ]

Beta blockers should not be used as a first-line treatment in the acute setting for cocaine-induced acute coronary syndrome (CIACS). No recent studies have been identified that show the benefit of beta blockers in reducing coronary vasospasm, or coronary vascular resistance, in patients with CIACS. In the multiple case studies identified, the use of beta blockers in CIACS resulted in detrimental outcomes, and the discontinuation of beta blockers used in the acute setting led to improvement in clinical course.[ citation needed ] The guidelines by the American College of Cardiology/American Heart Association also support this idea, and recommend against the use of beta blockers in cocaine-induced ST-segment elevation myocardial infarction (MI) because of the risk of coronary vasospasm.[ citation needed ] Though, in general, beta blockers improve mortality in patients who have suffered MI, it is unclear whether patients with CIACS will benefit from this mortality reduction because no studies assess the use of beta blockers in the long term, and because cocaine users may be prone to continue to abuse the substance, thus complicating the effect of drug therapy. [41] Contrast media are not contraindicated in patients receiving beta blockers. [42]

Toxicity

Glucagon, used in the treatment of overdose, [43] [44] increases the strength of heart contractions, increases intracellular cAMP, and decreases renal vascular resistance. It is, therefore, useful in patients with beta blocker cardiotoxicity. [45] [46] Cardiac pacing is usually reserved for patients unresponsive to pharmacological therapy.

People experiencing bronchospasm due to the β2 receptor-blocking effects of nonselective beta blockers may be treated with anticholinergic drugs, such as ipratropium, which are safer than beta agonists in patients with cardiovascular disease. Other antidotes for beta blocker poisoning are salbutamol and isoprenaline.

β-receptor antagonism

Stimulation of β1 receptors by epinephrine and norepinephrine induces a positive chronotropic and inotropic effect on the heart and increases cardiac conduction velocity and automaticity. [47] Stimulation of β1 receptors on the kidney causes renin release. [48] Stimulation of β2 receptors induces smooth muscle relaxation, [49] induces tremor in skeletal muscle, [50] and increases glycogenolysis in the liver and skeletal muscle. [51] Stimulation of β3 receptors induces lipolysis. [52]

Beta blockers inhibit these normal epinephrine- and norepinephrine-mediated sympathetic actions, [3] but have minimal effect on resting subjects.[ citation needed ] That is, they reduce the effect of excitement or physical exertion on heart rate and force of contraction, [53] and also tremor, [54] breakdown of glycogen, and dilation of bronchi. [55]

Since β2 adrenergic receptors can cause vascular smooth muscle dilation, beta blockers may cause some vasoconstriction. However, this effect tends to be small because the activity of β2 receptors is overshadowed by the more dominant vasoconstricting α1 receptors. By far the greatest effect of beta blockers remains in the heart. Newer, third-generation beta blockers can cause vasodilation through blockade of alpha-adrenergic receptors. [56]

Accordingly, nonselective beta blockers are expected to have antihypertensive effects. [57] The primary antihypertensive mechanism of beta blockers is unclear, but may involve reduction in cardiac output (due to negative chronotropic and inotropic effects). [58] It may also be due to reduction in renin release from the kidneys, and a central nervous system effect to reduce sympathetic activity (for those beta blockers that do cross the blood–brain barrier, e.g. propranolol).

Antianginal effects result from negative chronotropic and inotropic effects, which decrease cardiac workload and oxygen demand. Negative chronotropic properties of beta blockers allow the lifesaving property of heart rate control. Beta blockers are readily titrated to optimal rate control in many pathologic states.

The antiarrhythmic effects of beta blockers arise from sympathetic nervous system blockade—resulting in depression of sinus node function and atrioventricular node conduction, and prolonged atrial refractory periods. Sotalol, in particular, has additional antiarrhythmic properties and prolongs action potential duration through potassium channel blockade.

Blockade of the sympathetic nervous system on renin release leads to reduced aldosterone via the renin–angiotensin–aldosterone system, with a resultant decrease in blood pressure due to decreased sodium and water retention.

Intrinsic sympathomimetic activity

Also referred to as intrinsic sympathomimetic effect, this term is used particularly with beta blockers that can show both agonism and antagonism at a given beta receptor, depending on the concentration of the agent (beta blocker) and the concentration of the antagonized agent (usually an endogenous compound, such as norepinephrine). See partial agonist for a more general description.

Some beta blockers (e.g. oxprenolol, pindolol, penbutolol, labetalol and acebutolol) exhibit intrinsic sympathomimetic activity (ISA). These agents are capable of exerting low-level agonist activity at the β-adrenergic receptor while simultaneously acting as a receptor site antagonist. These agents, therefore, may be useful in individuals exhibiting excessive bradycardia with sustained beta blocker therapy.

Agents with ISA are not used after myocardial infarctions, as they have not been demonstrated to be beneficial. They may also be less effective than other beta blockers in the management of angina and tachyarrhythmia. [32]

α1-receptor antagonism

Some beta blockers (e.g., labetalol and carvedilol) exhibit mixed antagonism of both β- and α1-adrenergic receptors, which provides additional arteriolar vasodilating action.[ citation needed ]

Examples

Dichloroisoprenaline, the first beta blocker Dichloroisoprenaline.svg
Dichloroisoprenaline, the first beta blocker

Nonselective agents

Nonselective beta blockers display both β1 and β2 antagonism. [59]

β1-selective agents

β1-selective beta blockers are also known as cardioselective beta blockers. [59]

β2-selective agents

β3-selective agents

β1 selective antagonist and β3 agonist agents

Comparative information

Pharmacological differences

Indication differences

Propranolol is the only agent indicated for control of tremor, portal hypertension, and esophageal variceal bleeding, and used in conjunction with α-blocker therapy in phaeochromocytoma. [32]

Other effects

Beta blockers, due to their antagonism at beta-1 adrenergic receptors, inhibit both the synthesis of new melatonin and its secretion by the pineal gland. The neuropsychiatric side effects of some beta blockers (e.g. sleep disruption, insomnia) may be due to this effect. [77]

Some pre-clinical and clinical research suggests that some beta blockers may be beneficial for cancer treatment. [78] [79] [80] However, other studies do not show a correlation between cancer survival and beta blocker usage. [81] [82] Also, a 2017 meta-analysis failed to show any benefit for the use of beta blockers in breast cancer. [83]

Beta blockers have also been used for the treatment of schizoid personality disorder. [84]

See also

Related Research Articles

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used drugs are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

Metoprolol, marketed under the tradename Lopressor among others, is a medication of the selective β1 receptor blocker type. It is used to treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an abnormally fast heart rate. It is also used to prevent further heart problems after myocardial infarction and to prevent headaches in those with migraines.

Nadolol non-selective beta blocker used in the treatment of high blood pressure and chest pain

Nadolol, sold under the brand name Corgard among others, is a medication used to treat high blood pressure, heart pain, and atrial fibrillation. It has also been used to prevent migraine headaches and complications of cirrhosis. It is taken by mouth.

Betaxolol chemical compound

Betaxolol is a selective beta1 receptor blocker used in the treatment of hypertension and glaucoma. Being selective for beta1 receptors, it typically has fewer systemic side effects than non-selective beta-blockers, for example, not causing bronchospasm as timolol may. Betaxolol also shows greater affinity for beta1 receptors than metoprolol. In addition to its effect on the heart, betaxolol reduces the pressure within the eye. This effect is thought to be caused by reducing the production of the liquid within the eye. The precise mechanism of this effect is not known. The reduction in intraocular pressure reduces the risk of damage to the optic nerve and loss of vision in patients with elevated intraocular pressure due to glaucoma.

Isoprenaline chemical compound

Isoprenaline, or isoproterenol, is a medication used for the treatment of bradycardia, heart block, and rarely for asthma. It is a non-selective β adrenoreceptor agonist that is the isopropylamine analog of epinephrine (adrenaline).

Dobutamine chemical compound

Dobutamine is a medication used in the treatment of cardiogenic shock and severe heart failure. It may also be used in certain types of cardiac stress tests. It is given by injection into a vein or intraosseous as a continuous infusion. The amount of medication needs to be adjusted to the desired effect. Onset of effects is generally seen within 2 minutes.

Labetalol chemical compound

Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less preferred than a number of other blood pressure medications. It can be given by mouth or by injection into a vein.

Acebutolol chemical compound: beta blocker for treatment of hypertension and arrhythmias

Acebutolol, sold under the brand names Sectral among others, is a beta blocker for the treatment of hypertension and arrhythmias.

Bisoprolol Beta blocker family of medications and is of the β1 selective type.

Bisoprolol, marketed under the tradename Zebeta among others, is a medication most commonly used for heart diseases. This specifically includes high blood pressure, chest pain from not enough blood flow to the heart, and heart failure. It is taken by mouth.

Carvedilol chemical compound

Carvedilol, sold under the brand name Coreg among others, is a medication used to treat high blood pressure, congestive heart failure (CHF), and left ventricular dysfunction in people who are otherwise stable. For high blood pressure, it is generally a second-line treatment. It is taken by mouth.

Penbutolol chemical compound

Penbutolol is a medication in the class of beta blockers, used in the treatment of high blood pressure. Penbutolol is able to bind to both beta-1 adrenergic receptors and beta-2 adrenergic receptors, thus making it a non-selective β blocker. Penbutolol is a sympathomimetic drug with properties allowing it to act as a partial agonist at β adrenergic receptors.

Beta-1 adrenergic receptor protein-coding gene in the species Homo sapiens

The beta-1 adrenergic receptor, also known as ADRB1, is a beta-adrenergic receptor, and also denotes the human gene encoding it. It is a G-protein coupled receptor associated with the Gs heterotrimeric G-protein and is expressed predominantly in cardiac tissue.

Nebivolol chemical compound

Nebivolol is a beta blocker used to treat high blood pressure and heart failure. It is generally less preferred than a number of other blood pressure medications. It may be used by itself or with other blood pressure medication. It is taken by mouth.

Adrenergic antagonist drug that binds to but do not activate adrenergic receptors

An adrenergic antagonist is a drug that inhibits the function of adrenergic receptors. There are five adrenergic receptors, which are divided into two groups. The first group of receptors are the beta (β) adrenergic receptors. There are β1, β2, and β3 receptors. The second group contains the alpha (α) adrenoreceptors. There are only α1 and α2 receptors. Adrenergic receptors are located near the heart, kidneys, lungs, and gastrointestinal tract. There are also α-adreno receptors that are located on vascular smooth muscle.

A sympatholytic drug is a medication that opposes the downstream effects of postganglionic nerve firing in effector organs innervated by the sympathetic nervous system (SNS). They are indicated for various functions; for example, they may be used as antihypertensives. They are also used to treat anxiety, such as generalized anxiety disorder, panic disorder and PTSD.

Alpha blocker pharmaceutical drugs, neutral antagonist of alpha-adrenergic receptors

Alpha-blockers, also known as α-blockers or α-adrenoreceptor antagonists, are a class of pharmacological agents that act as antagonists on α-adrenergic receptors (α-adrenoceptors).

Beta-adrenergic agonist

Beta adrenergic agonists or beta agonists are medications that relax muscles of the airways, which widen the airways and result in easier breathing. They are a class of sympathomimetic agents which act upon the beta adrenoceptors. In general, pure beta-adrenergic agonists have the opposite function of beta blockers. Beta adrenoreceptor agonist ligands mimic the action of epinephrine and norepinephrine signaling in the heart, lungs, and smooth muscle tissue, with epinephrine expressing the highest affinity. The activation of β1, β2 and β3 activates the enzyme, adenylate cyclase. This, in turn, leads to the activation of the secondary messenger cyclic adenosine monophosphate (cAMP), cAMP then activates protein kinase A (PKA) which phosphorylates target proteins, ultimately inducing smooth muscle relaxation and contraction of the cardiac tissue.

Landiolol (INN) is an ultra short-acting, β1-superselective intravenous adrenergic antagonist, which decreases the heart rate effectively with less negative effect on blood pressure or myocardial contractility. In comparisson to other betablockers, landiolol has the shortest elimination half-life, ultra-rapid onset of effect, and predectible effectiveness with inactive metabolites. The pure S-enantiomer structure of landiolol is believed to develop less hypotensive side effects in comparison to other β-blockers. This has a positive impact on the treatment of patients when reduction of heart rate without decrease in arterial blood pressure is desired.. Landiolol was developed by modifying the chemical structure of esmolol to produce a compound with a higher rate of cardioselectivity and a greater potency without increasing its duration of action. It is sold as landiolol hydrochloride. Based on its positive benefit risk profile, landiolol has been granted the marketing authorization and introduced to the European markets under the brand names Rapibloc, Raploc, Runrapiq, Landibloc mid 2016. Landiolol is available in Japan under the brand names Onoact (50mg) and Corbeta.

Discovery and development of beta-blockers

β adrenergic receptor antagonists were initially developed in the 1960s, for the treatment of angina pectoris but are now also used for hypertension, congestive heart failure and certain arrhythmias. In the 1950s, dichloroisoproterenol (DCI) was discovered to be a β-antagonist that blocked the effects of sympathomimetic amines on bronchodilation, uterine relaxation and heart stimulation. Although DCI had no clinical utility, a change in the compound did provide a clinical candidate, pronethalol, which was introduced in 1962.

References

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